Our objective is to establish a highly interactive and dynamic group of investigators whose research focuses on understanding the functional role of epigenetic changes in human disease etiology and progression. We have proposed five new research projects all led by junior investigators, that will use molecular, biochemical, and computational biology approaches to study epigenetic regulation in different disease models. We will help define the role that environmental stressors play in disruption of the epigenome, and propose cutting edge, critical research in trans-generational models to understand how changes in the epigenomic may be linked to complex inheritance patterns and familial risk factors for high incidence diseases. These goals will be accomplished utilizing an integrative, systems biology approach to link epigenomic platforms such as global methylation arrays with next-generation RNA-sequencing and Chip-sequencing. To enhance the program further, we have included a translational component as a key facet of this COBRE, which is consistent with our global, strategic mission to address the needs of North Dakota's aging, largely rural population. Because epigenetic changes are potentially reversible, we believe that this research could lead to new treatment paradigms for devastating diseases such as cancer, drug addiction, and cardiovascular disease. The rationale for this center is that each individual brings unique expertise and key directions that together can help elucidate the role of epigenetic changes in various disease models. This center will nurture a focused group of investigators, and successful completion of our specific aims will result in the establishment of a collaborative and sustainable Center of Excellence in the Epigenomics of Development and Disease capable of attracting the brightest and most talented faculty, graduate students and postdoctoral fellows to conduct world class research in the burgeoning field of epigenetics. UND is fully committed to ensuring the growth and sustainability of this group even after the COBRE grant ends.